This is a new application for a NIDA Senior Scientist Award (K05). The candidate is William L. Woolverton, Ph.D., Professor of Psychiatry and Pharmacology at the University of Mississippi Medical Center (UMC). He has a 30-year history of drug abuse research and has been funded continuously by NIDA for the past 18 years. His primary area of research is intravenous drug self-administration by non-human primates. This animal model has played a central role in the evolution of our understanding of drug taking. The PI proposes to extend this model using novel approaches to examine in detail neurobiological and behavioral mechanisms that control drug taking. The proposed research reflects current grant support from NIDA. Neurobiological aims focus on the role of pharmacodynamic and pharmacokinetic mechanisms that determine the reinforcing effects of drugs that act at monoamine transporters. In addition, we will examine the possibility that self-administration of these compounds is partially determined by aversive effects that involve monoamine transporters or other neurotransmitter systems. Behavioral aims revolve around the hypothesis that loss of normal mechanisms controlling choice contributes to loss of control of drug self-administration, a defining feature of drug abuse. Drug choice will be examined in the context of major theoretical models of choice, including matching, delay discounting, and behavioral economics. Overall, this research will extend and refine our knowledge of neurobiological and behavioral determinants of drug taking. In addition, it will have important implications for the development of treatment medications, and suggest behavioral approaches to modifying the choice to self-administer a drug. This K05 will ensure that the candidate can concentrate his effort on his career as a drug abuse scientist. Continued career development will come from a combination of new research projects and new questions from previous projects, as well as to new and continuing collaborations. This will be facilitated by the large and active neuroscience community at UMC. Trainees at both pre- and postdoctoral levels will participate in this research program. An important goal will be to provide them with the skills needed for a career of research on the neurobehavioral pharmacology of drug self-administration. In addition, the candidate will continue to participate in other professional activities that contribute to overall career development, such as teaching and active membership on journal editorial boards, government advisory committees, and scientific organizations.